This scanning electron microscope image shows the yellow cells of the novel coronavirus that causes COVID-19 emerging from a lab culture medium. The image was captured and colorized at the National Institute of Allergy and Infectious Disease's Rocky Mountain Laboratories in Hamilton, Montana. Photo credit: NIAID-RML

As the novel coronavirus continues to spread throughout the world, keeping people and businesses in our communities and across the United States shuttered, the virus is clearly something to be feared.

But of the many viruses known to infect humans, what makes this one, which has caused the worst pandemic in a century, so dangerous?

The virus that causes COVID-19 is not the most deadly. Ebola kills upwards of 50% of people it infects. The coronaviruses that cause Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) result in death in about 10% of infections and between 30% to 40% of cases, respectively.

More deadly than the flu

Although scientists won’t know for sure until testing becomes widespread, COVID-19 could be about 10 times more deadly than the seasonal flu, which leads to death in about 0.1% of those it infects, says Donald N. Forthal, MD, professor of medicine and molecular biology and biochemistry, and chief of infectious diseases at UCI School of Medicine.

Researchers also don’t have accurate enough numbers to determine the actual percentage of deaths that result from this viral infection, given that there are a great many mild cases, as well as deaths, that have gone unreported.

But Forthal expects the mortality rate to be lower than what we’re seeing today in hotspots around the globe once the data are finally collected.

It’s not the most contagious virus, either.

Michael J. Buchmeier, PhD, professor of infectious diseases at UCI School of Medicine, explains that this virus, while deadly, is thought to be about as contagious as the seasonal flu, with one person infecting another two or three.

Contrast that with measles, where one person can infect 18, or chicken pox, where one person can infect 12. But these two highly contagious diseases are controlled by vaccination.

No one is immune

But it is a virus that has never been seen in humans, so absolutely no one is immune to it. That added to the fact that it spreads as easily from person to person as influenza, and infects the upper respiratory system, is what makes it so dangerous. Plus there is no vaccine.

Because the COVID-19 virus is found in the upper airway — including the mouth and nose — the infection can be spread through coughs, sneezes, huffing and puffing, and likely even loud talking, according to Forthal.

Moreover, we are learning that infected people are unknowingly spreading the virus days before they begin to experience symptoms. Some may not experience symptoms at all.

Neither SARS nor MERS spread as easily or widely.

This new virus "is capable of causing very severe disease,” Buchmeier says. 

Stickier than SARS-1

The virus that causes COVID-19 is similar to SARS — in fact, it’s officially called SARS-CoV-2 — and it attaches to the same receptors as SARS-CoV-1, but it’s stickier, Buchmeier explains. That allows the virus to enter cells more quickly, get a firmer grasp and begin spreading more quickly throughout the body.

This virus also attacks the lower respiratory tract — the bronchial tubes and the lungs — where it can lead to pneumonia.

That triggers an inflammatory response as the body attempts to fight the invader. In some people — about 15% — this immune response starts a cyclical overreaction of the body’s immune system called a cytokine storm.

“Cytokine production is a normal immune response to try to kill the virus,” Forthal says. “Under normal circumstances, the response peaks early, clears the virus and helps produce antibodies and T cells specific for the virus. But in some COVID-19 patients, the cytokine response sticks around too long and too strongly.”

“You not only get severe damage to the lungs, which may or may not be directly attributable to the virus,” says Forthal. “But the cytokine storm also can contribute to coagulopathy [clot formation], kidney damage and heart damage.”

This is what’s causing some people to become severely ill or die, Forthal says. Researchers have seen other coronaviruses provoke similar cytokine overreactions.

Age, sex, chronic conditions increase risk

Forthal says mortality increases with age, with the highest case-fatality rates being observed in people over 70. “Children rarely have severe disease.”

Obesity and other chronic conditions — such as high blood pressure, diabetes and underlying heart, lung and kidney disease — increase the risk of severe infection, Forthal says.

The prevalence of these diseases among older people, who may lack strength owing to aging and the inability of some people with dementia to relate the symptoms they’re experiencing, add to the devastating impact the virus is having in nursing and care homes.

Gender is another risk factor for COVID-19. Men are dying at higher rates than women. While doctors don’t yet know why, research has shown similar patterns of cytokine overreactions based on age and gender with other coronaviruses.

A reason for hope

“Not everyone responds in the same way,” says Buchmeier. “The fact that children don’t typically have severe disease shows us that [our bodies] are capable of clearing this virus, if they don’t develop pneumonia.”

Forthal and Buchmeier, who are members of the UC Irvine Center for Virus Research, agree that remdesivir, a drug now in the news and the subject of a UCI Health clinical trial, looks promising as a treatment for COVID-19. They also are confident that treatment will improve as researchers and clinicians gain more experience with the disease.

While work is proceeding at warp speed to develop a vaccine to protect against COVID-19, for now both scientists say testing to map its spread and allow for its containment is essential.